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Everyday News-Gene Therapy May Thwart HIV
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This past year, a Berlin man, Timothy Brown, became world famous as the first—and thus far only—person to apparently have been cured of his HIV infection. Brown's HIV disappeared after he developed leukemia and doctors gave him repeated blood transfusions from a donor who harbored a mutated version of a receptor the virus uses to enter cells. Now, researchers report promising results from two small gene-therapy studies that mimic this strategy, hinting that the field may be moving closer to a cure that works for the masses. At the Interscience Conference on Antimicrobial Agents and Chemotherapy in Chicago, Illinois, this weekend, researchers reported preliminary results from tests of a novel treatment in 15 HIV-infected people designed to free them from the need to take antiretroviral drugs. The studies, conducted separately on the East and West coasts of the United States, attempt to make the immune system resistant to HIV by crippling a receptor, known as CCR5, on T cells that the virus uses during the infection process. The man who donated blood for Timothy Brown's transfusions had naturally defective CCR5 receptors. The trial participants had T cells removed from their blood and then modified in the laboratory with a designer enzyme engineered by Sangamo BioSciences in Richmond, California. The enzyme, called a zinc finger nuclease, clips the gene for the CCR5 receptor and disables it. Ten billion modified cells were then reinfused into the participants' bodies, and the new data show that about 25% of cells had the mutant CCR5s. The studies found that modified T cells persisted for more than 6 months in several patients. In one provocative case reported in Chicago yesterday, a patient who received the gene therapy and then stopped taking antiretroviral drugs had HIV return within a month, as typically happens when people interrupt their treatment. But a few weeks later, the virus began to decline, and it dropped to undetectable levels in concert with evidence that the gene therapy had altered his T cells. "Those kinetics are very different from what I've seen in treatment interruption studies, and we've done many," says Pablo Tebas, an infectious disease clinician at the University of Pennsylvania who heads the East Coast study of six participants. "This patient goes down, way down." Tebas recognizes that his study is uncontrolled and that they've seen this response in only one patient. What's more, the patient already had a natural advantage because he has a crippled CCR5 gene in one of the two copies he inherited. Tebas suspects that the gene therapy coupled with his natural CCR5 mutation combined to lead to the dramatic result. "This is a very small experiment, and I don't think it's a cure by any means, but the Berlin patient is only one patient, and it changed research priorities," Tebas says. "This shows that there's a correlation between antiviral activity and the proportion of modified cells. It shows a path forward." Although researchers do not expect the gene therapy to entirely clear HIV from the body, they hope it will create a "functional cure"—in other words, contain the virus to such a powerful extent that people no longer need antiretrovirals. Virologist David Margolis, who is conducting his own HIV cure studies at the University of North Carolina, Chapel Hill, says many questions remain about the impact of this gene therapy, however. "These data are interesting, and encouraging, but still incomplete," he says. Yet Margolis is "impressed" by the percentage of cells that have the artificially modified CCR5 gene. Even if this gene therapy proves itself, the cost and technical challenge of the intervention means it likely will have little chance of being used outside of wealthy countries. But Tebas notes that the cost of antiretrovirals also is high and that any calculation would have to balance one against the other.  |
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